Bacterial infections of the lung are common at all ages but especially at the extremes of life. Knowledge of normal pulmonary host defense mechanisms are incomplete, in general, and the early developmental aspects of those defenses in particular have not been well-defined. The present studies are aimed at defining better the manner in which bacteria that are inhaled into the lung are killed. Specifically, the studies are designed to evaluate the role of extracellular antibacterial lipids, which have recently been demonstrated in the surfactant of rat alveolar lining material, in pulmonary bacterial clearance. The development of antibacterial lipids will be examined quantitatively and qualitatively from birth to adulthood in a murine model, and the biochemical identity of the antibacterial factors (presumably free fatty acids) will be established using standard techniques. The ability of the developing murine lung to clear inhaled pyogenic bacteria (and particularly pneumococci) will be studied from birth to adulthood. The pulmonary clearance of these bacteria will be tested in a manner that will define the role of extracellular bactericidal factors in clearance. For this purpose, bacterial variants which have been selected for their resistance in vitro to the antibacterial lipids of rat surfactant will be compared with their "wild" parent strains in standard models of bacterial clearance in rats. Developmental aspects of clearance will be emphasized and the results obtained in vivo will be correlated with the results of bronchoalveolar lavage for detection of antibacterial lipids at different stages of development. The effects of antibacterial lipids on opson-phagocytosis and intra-cellular killing of selected bacteria by adherent rat alveolar macrophages will be studied in vitro, using animals at various stages of development. It seems important that alveolar macrophage bactericidal function be evaluated in terms of the lipid components of the alveolar microenvironment because these elements co-exist in vivo. Similarly, because antibacterial lipids of rat surfactant can affect bacterial cellular integrity, interactions of these lipids and other bacteriolytic substances such as the complement cascade and lysozyme will be studied. In summary, the goal of the proposed studies is to expand our knowledge of pulmonary host defenses in the early developmental period, emphasizing the role of extracellular factors as well as cellular factors in the clearance of bacterial pathogens.